The goal of this research is to evaluate the role of free fatty acids in macrophage-mediated destruction of tumor cells. It has been found that macrophages from animals treated with the attenuated BCG strain of Mycobacterium tuberculosis are cytotoxic for transformed but not for normal cells, whereas macrophages from normal animals are not cytotoxic for either cell type. These results indicate that the mechanism of tumor cell destruction by macrophages is dependent upon alterations in both the target and the effector cells. Our preliminary findings indicate that activated macrophages contain elevated levels of free fatty acids and that these fatty acids exert a greater cytotoxic effect on transformed cells than on normal cells, especially in the period following a short-term exposure to the fatty acid. The aims of the proposed study are to 1) pinpoint the lesion which fatty acids create in transformed cells, and 2) determine the pathways through which activated macrophages produce and express their elevated free fatty acid levels.